Please use this identifier to cite or link to this item:
https://hdl.handle.net/2440/135497
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Type: | Journal article |
Title: | Pneumococcal Phasevarions Control Multiple Virulence Traits, Including Vaccine Candidate Expression |
Author: | Phillips, Z.N. Trappetti, C. Van Den Bergh, A. Martin, G. Calcutt, A. Ozberk, V. Guillon, P. Pandey, M. von Itzstein, M. Swords, W.E. Paton, J.C. Jennings, M.P. Atack, J.M. |
Citation: | Microbiology Spectrum, 2022; 10(3):1-17 |
Publisher: | American Society for Microbiology |
Issue Date: | 2022 |
ISSN: | 2165-0497 2165-0497 |
Editor: | LaRock, C.N. |
Statement of Responsibility: | Zachary N. Phillips, Claudia Trappetti, Annelies Van Den Bergh, Gael Martin, Ainslie Calcutt, Victoria Ozberk, Patrice Guillon, Manisha Pandey, Mark von Itzstein, W. Edward Swords, James C. Paton, Michael P. Jennings, John M. Atack |
Abstract: | Streptococcus pneumoniae is the most common cause of bacterial illness worldwide. Current vaccines based on the polysaccharide capsule are only effective against a limited number of the .100 capsular serotypes. A universal vaccine based on conserved protein antigens requires a thorough understanding of gene expression in S. pneumoniae. All S. pneumoniae strains encode the SpnIII Restriction-Modification system. This system contains a phase-variable methyltransferase that switches specificity, and controls expression of multiple genes—a phasevarion. We examined the role of this phasevarion during pneumococcal pathobiology, and determined if phase variation resulted in differences in expression of currently investigated conserved protein antigens. Using locked strains that express a single methyltransferase specificity, we found differences in clinically relevant traits, including survival in blood, and adherence to and invasion of human cells. We also observed differences in expression of numerous proteinaceous vaccine candidates, which complicates selection of antigens for inclusion in a universal protein-based pneumococcal vaccine. This study will inform vaccine design against S. pneumoniae by ensuring only stably expressed candidates are included in a rationally designed vaccine. |
Keywords: | phasevarion phase variation Streptococcus pneumoniae vaccine epigenetic regulation pneumococcus |
Description: | Published online 10 May 2022 |
Rights: | Copyright © 2022 Phillips et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license. |
DOI: | 10.1128/spectrum.00916-22 |
Grant ID: | http://purl.org/au-research/grants/arc/DP180100976 http://purl.org/au-research/grants/arc/DP190102980 http://purl.org/au-research/grants/nhmrc/1071659 http://purl.org/au-research/grants/nhmrc/1174876 http://purl.org/au-research/grants/nhmrc/1138466 http://purl.org/au-research/grants/nhmrc/1160379 |
Published version: | http://dx.doi.org/10.1128/spectrum.00916-22 |
Appears in Collections: | Microbiology and Immunology publications |
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hdl_135497.pdf | Published version | 1.54 MB | Adobe PDF | View/Open |
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